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Molecular Imaging and Biology

, Volume 20, Issue 4, pp 667–681 | Cite as

[11C]Harmine Binding to Brain Monoamine Oxidase A: Test-Retest Properties and Noninvasive Quantification

  • Francesca Zanderigo
  • Alexandra E. D’Agostino
  • Nandita Joshi
  • Martin Schain
  • Dileep Kumar
  • Ramin V. Parsey
  • Christine DeLorenzo
  • J. John Mann
Research Article
  • 143 Downloads

Abstract

Purpose

Inhibition of the isoform A of monoamine oxidase (MAO-A), a mitochondrial enzyme catalyzing deamination of monoamine neurotransmitters, is useful in treatment of depression and anxiety disorders. [11C]harmine, a MAO-A PET radioligand, has been used to study mood disorders and antidepressant treatment. However, [11C]harmine binding test-retest characteristics have to date only been partially investigated. Furthermore, since MAO-A is ubiquitously expressed, no reference region is available, thus requiring arterial blood sampling during PET scanning. Here, we investigate [11C]harmine binding measurements test-retest properties; assess effects of using a minimally invasive input function estimation on binding quantification and repeatability; and explore binding potentials estimation using a reference region-free approach.

Procedures

Quantification of [11C]harmine distribution volume (VT) via kinetic models and graphical analyses was compared based on absolute test-retest percent difference (TRPD), intraclass correlation coefficient (ICC), and identifiability. The optimal procedure was also used with a simultaneously estimated input function in place of the measured curve. Lastly, an approach for binding potentials quantification in absence of a reference region was evaluated.

Results

[11C]harmine VT estimates quantified using arterial blood and kinetic modeling showed average absolute TRPD values of 7.7 to 15.6 %, and ICC values between 0.56 and 0.86, across brain regions. Using simultaneous estimation (SIME) of input function resulted in VT estimates close to those obtained using arterial input function (r = 0.951, slope = 1.073, intercept = − 1.037), with numerically but not statistically higher test-retest difference (range 16.6 to 22.0 %), but with overall poor ICC values, between 0.30 and 0.57.

Conclusions

Prospective studies using [11C]harmine are possible given its test-retest repeatability when binding is quantified using arterial blood. Results with SIME of input function show potential for simplifying data acquisition by replacing arterial catheterization with one arterial blood sample at 20 min post-injection. Estimation of [11C]harmine binding potentials remains a challenge that warrants further investigation.

Key words

Positron emission tomography Brain Monoamine oxidase A Repeatability Noninvasive estimation 

Notes

Acknowledgements

The authors would like to thank Dr. Rajan Murthy for his help with the protocol used to acquire the scans.

Funding Information

This research was supported by 5P50MH062185, Conte Center: The Neurobiology of Suicidal Behavior (National Institute for Mental Health) (PI: Mann).

Compliance with Ethical Standards

Conflicts of Interest

Drs. Zanderigo, D’Agostino, Schain, Kumar, Parsey, and Delorenzo, and Ms. Joshi declare no conflicts of interest. Dr. Mann receives royalties for commercial use of the Columbia-Suicide Severity Rating Scales from the Research Foundation for Mental Hygiene.

Supplementary material

11307_2018_1165_MOESM1_ESM.pdf (573 kb)
ESM 1 (PDF 573 kb)

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Copyright information

© World Molecular Imaging Society 2018

Authors and Affiliations

  1. 1.Department of PsychiatryColumbia UniversityNew YorkUSA
  2. 2.Molecular Imaging and Neuropathology DivisionNew York State Psychiatric InstituteNew YorkUSA
  3. 3.Now at Department of PsychiatryStony Brook UniversityStony BrookUSA
  4. 4.Department of Electrical and Computer EngineeringStony Brook UniversityStony BrookUSA
  5. 5.Department of RadiologyColumbia UniversityNew YorkUSA

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